Zelapar

OVERDOSE

Selegiline

No specific information is available about clinically
significant overdoses with swallowed selegiline or ZELAPAR. However, experience
gained during development of the 5 mg swallowed dosage form reveals that some
individuals exposed to doses of 600 mg of d,l-selegiline suffered severe
hypotension and psychomotor agitation.

Since the selective inhibition of MAO-B by ZELAPAR is
achieved only at doses in the range recommended for the treatment of
Parkinson's disease (e.g., 2.5 mg/day), overdoses are likely to cause
significant inhibition of both MAO-A and MAO-B. Consequently, the signs and
symptoms of overdose may resemble those observed with marketed non-selective
MAO inhibitors [e.g., tranylcypromine (PARNATE®), isocarboxazid
(MARPLAN®), and phenelzine (NARDIL®)]. For this reason,
in cases of overdose with selegiline, dietary tyramine restriction should be
observed for several weeks to avoid the risk of a hypertensive reaction.

Overdose With Non-Selective MAO Inhibitors

NOTE: The following description of presenting symptoms
and clinical course is based upon overdose descriptions of nonselective MAO
inhibitors and does not include information from patients who have overdosed on
oral selegiline or ZELAPAR.

Characteristically, signs and symptoms of non-selective
MAO inhibitor overdose may not appear immediately. Delays of up to 12 hours
between ingestion of drug and the appearance of signs may occur. Importantly,
the peak intensity of the syndrome may not be reached for upwards of a day
following the overdose. Death has been reported following overdosage.
Therefore, immediate hospitalization, with continuous patient observation and
monitoring for a period of at least two days following the ingestion of such
drugs in overdose, is strongly recommended.

The clinical picture of MAO inhibitor overdose varies
considerably; its severity may be a function of the amount of drug consumed.
The central nervous and cardiovascular systems are prominently involved.

Treatment Or Management Of Overdose

Treatment of overdose with non-selective MAO inhibitors
is symptomatic and supportive. Induction of emesis or gastric lavage with
instillation of charcoal slurry may be helpful in early poisoning, provided the
airway has been protected against aspiration. Signs and symptoms of central
nervous system stimulation, including convulsions, should be treated with
diazepam, given slowly intravenously. Phenothiazine derivatives and central
nervous system stimulants should be avoided. Hypotension and vascular collapse
should be treated with intravenous fluids and, if necessary, blood pressure
titration with an intravenous infusion of a dilute pressor agent. It should be
noted that adrenergic agents may produce a markedly increased pressor response.

Support respiration, including management of the airway,
use of supplemental oxygen, and mechanical ventilatory assistance, as required.

Body temperature should be monitored closely. Intensive
management of hyperpyrexia may be required. Maintenance of fluid and
electrolyte balance is essential.

CONTRAINDICATIONS

ZELAPAR is contraindicated in patients using meperidine,
tramadol, methadone, or propoxyphene. Serotonin syndrome, a potentially serious
condition, which can result in death, has been reported with concomitant use of
meperidine (e.g., Demerol and other trade names). At least 14 days should
elapse between discontinuation of ZELAPAR and initiation of treatment with
these medications [see WARNINGS AND PRECAUTIONS].

ZELAPAR is contraindicated in patients on any other MAO
inhibitor (selective or nonselective), because of an increased risk for
hypertensive crisis. At least 14 days should elapse between discontinuation of
ZELAPAR and initiation of treatment with any MAO inhibitor.

ZELAPAR is contraindicated in patients using St. John's
wort, or cyclobenzaprine (a tricyclic muscle relaxant).